A first-in-human study to investigate safety, tolerability, and pharmacokinetics of single and multiple ascending doses of JZP505 in healthy adult participants
| ISRCTN | ISRCTN40371122 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN40371122 |
| Integrated Research Application System (IRAS) | 1006698 |
| Sponsor | JAZZ Pharmaceuticals Research UK Ltd |
| Funder | JAZZ Pharmaceuticals Research UK Ltd |
- Submission date
- 26/06/2024
- Registration date
- 27/06/2024
- Last edited
- 24/07/2026
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Plain English summary of protocol
Background and study aims
This is a clinical study of an investigational drug called JZP505. An investigational drug has not yet been approved for doctors to prescribe. This is a "first-in-human" study, meaning it is the first time JZP505 has been given to people, although it has been tested in animals.
The main goals of this study are to learn more about:
-The safety of the study drug and any possible side effects.
-How the body takes in and gets rid of the study drug (this is called pharmacokinetics).
-Whether taking the study drug with food changes how it works.
-How the study drug affects the brain, including any changes to mood, sleepiness, or brain wave activity (which is measured with a test called an EEG).
Who can participate?
The study is looking for about 96 healthy volunteers. Participants can be male or female and must be between 18 and 55 years old. To be in the study, participants must be in good health and meet certain guidelines, such as having a healthy weight for their height.
For safety reasons, some people cannot join the study. This includes people who have had thoughts of self-harm, serious allergies, or certain kidney or heart problems. There are also rules about lifestyle, such as not using cannabis or tobacco products for 3 months before the study.
What does the study involve?
This is a randomly allocated, double-blind, placebo-controlled study. Randomization means that participants are chosen by chance (like flipping a coin) to get either JZP505 or a placebo. A placebo is a substance that looks like the study drug but contains no active ingredient. Double-blind means that neither the participant nor the study doctor will know who is getting the real drug and who is getting the placebo.
The study has two parts:
Part A (Single Dose): Participants will get one dose of the study drug or placebo. This part requires staying at the study clinic for 5 days.
Part B (Multiple Doses): Participants will get a dose of the study drug or placebo every day for 7 days. This part requires staying at the clinic for 11 days.
In total, being in the study will last between 5 and 8 weeks. While at the clinic, participants will have many health checks, including physical exams, blood and urine tests, and tests to check their heart (ECG) and brain (EEG) activity.
What are the possible benefits and risks of participating?
Benefits: Since this study is for healthy people, there are no direct medical benefits to joining. However, the information we learn might help develop a new medicine for others in the future.
Risks: Because this is the first time JZP505 is being given to people, there could be side effects that we don't know about yet. Based on what we know so far, possible risks could include:
-Injury to the liver. This will be monitored with regular blood tests.
-Feeling drowsy, sleepy, or tired
-Thoughts of self-harm. This will be monitored by asking questions about mood
-A serious allergic reaction
The study tests themselves may have risks, like bruising from a blood draw or skin irritation from the test sensors.
Where is the study run from?
The research clinic is Labcorp Clinical Research Unit, formerly Fortrea, Leeds, England.
When is the study starting and how long is it expected to run for?
April 2023 to January 2024.
Who is funding the study?
GW Research Ltd / JAZZ Pharmaceuticals Research UK Ltd.
Who is the main contact?
Clinical Trial Disclosure and Transparency, ClinicalTrialDisclosure@jazzpharma.com
Contact information
Public, Scientific
Building 730, Kent Science Park, Sittingbourne
Kent
ME9 8AG
United Kingdom
| ClinicalTrialDisclosure@jazzpharma.com |
Principal investigator
Drapers Yard, Marshall Street
Leeds
LS11 9EH
United Kingdom
| Phone | +441133013644 |
|---|---|
| jim.bush@fortrea.com |
Study information
| Primary study design | Interventional |
|---|---|
| Allocation | Randomized controlled trial |
| Masking | Blinded (masking used) |
| Control | Placebo |
| Assignment | Sequential cohort, parallel design |
| Purpose | Treatment |
| Scientific title | A phase 1, first-in-human, randomized, double-blind, placebo-controlled, safety, tolerability, and pharmacokinetic study with single and multiple ascending doses and food effect of JZP505 in healthy adult participants |
| Study objectives | 1. Safety 2.Tolerability 3. Pharmacokinetics |
| Ethics approval(s) |
1. Approved 19/01/2023, London-Brent Research Ethic Committee (80 London Road, Skipton House, London, SE1 6LH, United Kingdom; +44 (0)20 3080 6456; brent_rec@hra.nhs.uk), ref: 22/LO/0850 2. Approved 07/03/2023, MHRA (10 South Colonnade, Canary Wharf, London, E14 4PU, United Kingdom; +44 (0)20 3080 6456; clintrialhelpline@mhra.gov.uk), ref: CTA 36772/0031/001-0001 |
| Health condition(s) or problem(s) studied | Healthy volunteers |
| Intervention | Experimental Drug: JZP505 Control Drug: Placebo A single-site, randomized (by computer), double-blind, single-ascending dose (SAD) and multiple-ascending dose (MAD) study of JZP505 will be conducted in 2 parts (Part A: SAD + food effect; Part B: MAD) Dosing: SAD: Single oral doses of JZP505 or placebo (150mg-2400mg) Food Effect: Two single oral doses of JZP505 or placebo in fasted and fed states in Cohort A2 (300mg) MAD: Once or twice daily oral dosing of JZP505 or placebo for 7 days (200mg-1000mg) Cohorts: SAD: 7 (Cohorts A1 to A7) SAD Food Effect: Cohort A2 (fed and fasted) MAD: 5 (Cohorts B1 to B5) |
| Intervention type | Drug |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | JZP505 |
| Primary outcome measure(s) |
1. Part A: Incidence and severity of treatment-emergent adverse events (TEAEs) measured using the number of participants at Day 1 up to 9 months |
| Key secondary outcome measure(s) |
1. Part A: Dose proportionality of JZP505 for Cmax measured using ng/mL at Day 1 |
| Completion date | 12/01/2024 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 55 Years |
| Sex | All |
| Target sample size at registration | 96 |
| Total final enrolment | 55 |
| Key inclusion criteria | Age 1. Is 18 to 55 years of age inclusive at the time of signing the informed consent Type of Participant and Disease Characteristics 2. Are overtly healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring Weight 3. Has a minimum body weight of 50 kg and a BMI within the range 18.5 to 32 kg/m2, inclusive 4. Is male or female: 4.1. Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 90 days after the last dose of study intervention: 4.1.1. Refrain from donating sperm. PLUS either of the following: 4.1.2. Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR 4.1.3. Use contraception/barrier as follows: 4.1.3.1. Use a male condom with female partner use of an additional highly effective contraceptive method with a failure rate of < 1% per year as described in Contraceptive and Barrier Requirements when having sexual intercourse with a WOCBP who is not currently pregnant 4.1.3.2. Agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person 4.2. Female participants are eligible to participate if: 4.2.1. She is a WONCBP, as defined in Contraceptive and Barrier Guidance Informed Consent 5. Is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol |
| Key exclusion criteria | Medical Conditions 1. Any history of suicidal behavior or any suicidal ideation, as indicated by a positive response to Item 4 or Item 5 on the C-SSRS, or past or current history of self-harm thoughts or actions as identified on C-SSRS at screening 2. Presence or history of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, as determined by the investigator (or designee); any known or suspected hypersensitivity to cannabinoids, or any of the excipients of JZP505. Hay fever is allowed unless it is active 3. Presence of congenital nonhemolytic hyperbilirubinemia (eg, Gilbert’s syndrome) at either screening or admission on Day –1, as assessed by the investigator (or designee) 4. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs 5. History of drug abuse within 2 years of screening or current habituation to any medications or illegal drugs 6. Any history of fits/seizures (apart from childhood febrile convulsions before the age of 6 years). Known or suspected history or family history of schizophrenia or other psychotic illness; history of severe personality disorder or other significant psychiatric disorder 7. Poor peripheral venous access 8. Clinically significant renal disease, nephrectomy, renal transplant or estimated glomerular filtration rate of < 60 mL/min/1.73 m2 at screening based on the MDRD equation Prior/Concomitant Therapy 9. Use or intend to use any prescription medications or nonprescription drugs within 14 days or 5 half-lives, whichever is longer, prior to Check-in on Day –1 Prior/Concurrent Clinical Study Experience 10. Participation in a clinical trial involving administration of a study intervention (new chemical entity) in the past 3 months. Diagnostic Assessments 11. Positive serology panel (including hepatitis B surface antigen and hepatitis C virus antibody) and/or positive human immunodeficiency virus antibody/p24 antigen screens 12. Positive alcohol breath test result, cotinine test, or positive urine drug screen (may be confirmed by repeat) at screening or Check-in on Day –1 13. Participant has impaired hepatic function at screening or Check-in on Day −1 (confirmed by repeat assessment), defined as any of the following: 13.1. Serum ALT or AST > 1.0 × ULN 13.2. TBL > ULN 13.3. INR > ULN 13.4. Serum creatinine > 1 × ULN 14. Hemoglobin level < 13.5 g/dL (male participants) or < 12.5 g/dL (female participants) at screening or Check-in on Day ─1 15. Absolute neutrophil count < 2 × 109/dL at screening or Check-in on Day ─1 16. Participants with a supine systolic blood pressure at screening of < 90 mmHg (or > 140 mmHg) or a diastolic blood pressure of < 50 mmHg (or > 90 mmHg), confirmed by repeat readings 17. Participants with an orthostatic decrease in systolic blood pressure > 20 mmHg, or a decrease in diastolic blood pressure >10 mmHg upon standing 18. Clinically significant ECG abnormality at screening (confirmed by repeat within 2 hours), including, but not limited to: 18.1. PR interval > 220 msec 18.2. QRS duration > 120 msec 18.3. Complete left or right bundle branch block, second- or third-degree heart block 18.4. QTcF > 450 msec for male participants or > 470 msec for female participants; the ECG may be repeated up to 2 times at the investigator’s discretion for confirmation (with 2 of 3 ECGs being below the threshold) 18.5. History of additional risk factors for torsade de pointes (eg, heart failure, clinically significant hypokalemia [< 2.5 mmol/L]) 18.6. Family history of long QT syndrome 18.7. Evidence of prior myocardial infarction 18.8. Clinically significant ST segment or T wave abnormalities or any other abnormality that is clinically significant in the investigator’s opinion or precludes accurate interpretation and calculations of cardiac intervals (eg, QRS) Other Exclusions 19. Receipt of blood products within 2 months prior to Check-in on Day –1. Donation or loss of blood (≥ 450 mL) from 3 months prior to screening, plasma from 2 weeks prior to screening, or platelets from 6 weeks prior to screening 20. Participant has been vaccinated within 28 days prior to admission on Day –1 and/or plans to obtain a vaccination during the trial 21. Participant is currently using or has used cannabis (recreational or medicinal), synthetic CBD-based medications within the 3 months prior to screening, or cannabinoid-based medications (eg, dronabinol and nabilone) within 30 days of trial entry or is unwilling to abstain for the duration of the trial 22. Alcohol consumption of > 21 units per week (males) or > 14 units per week (females). One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or ⅙ gill (25 mL) of spirits 23. Use of tobacco- or nicotine-containing products within 3 months prior to Check-in on Day –1 |
| Date of first enrolment | 18/04/2023 |
| Date of final enrolment | 12/01/2024 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
Holbeck
Leeds
LS11 9EH
England
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|
Editorial Notes
24/07/2026: The following updates were made to publish the study's full dataset:
1. The public and scientific titles were updated from "Phase 1 Trial: Fortrea".
2. Study objectives, allocation, masking, control, assignment, purpose, interventions and drug names were added.
3. Primary and key secondary outcomes were added.
4. Key inclusion and exclusion criteria were added.
5. Final enrolment number was added.
6. The plain English summary of the protocol was added.
7. The study contacts were amended.
27/06/2024: Study's existence confirmed by the Health Research Authority (HRA) London-Brent Research Ethics Committee.
